This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To develop a new cancer therapeutic, which would be able to suppress growth of cancer cells by specifically attacking the Warburg effect, we have chosen PFKFB3 as the therapeutic target protein molecule. To find lead compounds, we have performed virtual drug screening using 1.1 million database compounds and found ~200 positives. A further experimental screening reduced the pool to 9 actives. These 9 compounds exhibited inhibition of PFKFB3 activity more than 90% in their concentrations less than 10 uM. To optimize these compounds as more drug-like, it is necessary to have their structure/activity relationships (SAR) at the molecular level. To acquire the molecular SAR information, we are investigating the crystal structures of PFKFB3 in complex with these 9 compounds.